The effects of mercury on muscarinic cholinergic receptor subtypes (M1 and M2) in captive mink

A combination of in vitro (competitive binding assays) and in vivo (tissues from animals exposed to dietary methyl mercury, MeHg) experimental procedures was employed to assess the effects of mercury (MeHg, HgCl2) on the two-key muscarinic cholinergic, (mACh) receptor subtypes (M1, M2) in two brain regions (occipital cortex, brain stem) of captive mink (Mustela vison). In vitro, HgCl2 and MeHg were equipotent in inhibiting [H-3]-pirenzipine binding to the M1 receptor in the occipital cortex, but in the brain stem, MeHg was about 65 x more potent than HgCl2. For the M2 receptor, both HgCl2 and MeHg were more potent at inhibiting [H-3]-AFDX-384 binding in the occipital cortex than in the brain stem. Within each brain region, HgCl2 was more potent at inhibiting [H-3]-AFDX-384 binding than MeHg. In vivo exposure of captive mink to MeHg (0.5, 1, and 2 ppm MeHg in the diet for 89 days) resulted in greater binding of radioligands to the M1 and M2 receptor in the occipital cortex, but not in the brain stem, when compared to control animals. Based on the in vitro results, we could not conclude which mACh receptor subtype or brain region was most sensitive to Hg, but the in vivo findings suggest that Hg preferentially affects mACh receptor subtype (M1 and M2) levels in the occipital cortex. By studying distinct mACh receptors, these results extend upon previous studies in laboratory rodents and wildlife that showed Hg to affect the global population of mACh receptors. (C) 2008 Elsevier Inc. All rights reserved.